Body's 'Marijuana' May Be Key to Diet Pill

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A dreamy diet pill that someday allows people to eat as much as
they want without gaining weight seems possible, based on new
research into certain brain chemicals that influence how quickly
we burn fat.

Scientists used lab mice to turn down brain levels of
endocannabinoids, chemicals produced by our bodies that are
similar in molecular structure to the active ingredients in
marijuana.

Previous research has found that endocannabinoids play an
important role in
regulating energy metabolism. In the new study, blocking the
activity of endocannabinoids in the brain enabled mice to stay
skinny without exercise or dieting. The researchers explained
that the mice were in a "hypermetabolic state," in which their
bodies were using up energy (that is, calories) at a much higher
rate than normal.

"We discovered that these mice were resistant to obesity because
they
burned fat calories much more efficiently than normal mice
do," study researcher Daniele Piomelli, a professor at the
University of California, Irvine, said in a statement. "We had
known that
endocannabinoids play a critical role in cell energy
regulation, but this is the first time we found a target where
this occurs."

This target is a compound called 2-AG, found in high levels in
mammalian brains, and researchers think it plays a role in the
brain circuits controlling how the body uses energy, which we get
from food.

A previous study by Piomelli found these compounds
make us crave fat. To see if lowering the levels of these
compounds had the opposite effect, Piomelli engineered the brain
cells of mice to express only low levels of this compound, then
compared the animals' behavior and health with that of normal
mice.

The modified mice ate more and moved less than their normal
counterparts, but stayed skinny even on a high-fat diet. Not only
did they look healthy, they had normal blood pressure, and no
increased risk of heart disease and diabetes that usually come
with a high-fat diet.

The researchers determined that the modified mice's
brown fat was overactive — it was being turned into heat much
quicker than in the normal mice. Brown fat is a type of fat that
keeps mammals warm, and this heat creation burns off excess
energy.

Jumping from lab studies in mice to actual health benefits for
humans is still a ways away, though, since it is difficult to
make a drug that acts only in one brain area.

"To produce the desired effects, we would need to create a drug
that blocks 2-AG production in the brain, something we're not yet
able to do," Piomelli said. "So don't cancel that gym membership
just yet."

The study was published today (March 6) in the journal Cell
Metabolism.

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